Stomatitis is a disease that affects oral mucosa. Specifically, stomatitis is an inflammation which is caused or exacerbated by pharmaceutical treatment, specifically by a chemotherapeutic or radioactive treatment, and in some cases, is accompanied by an ulcer(s). Stomatitis exhibits mild to severe symptoms. Patients suffering from severe stomatitis cannot eat food through their mouth. Meanwhile, erythematous mucositis, which is a type of stomatitis, appears within three days, more commonly within 5-7 days after exposure to a chemotherapeutic or radioactive treatment. Erythematous mucositis can progress to an ulcerative mucositis within 7 days after exposure to a chemotherapeutic treatment in general and some erythematous mucositises can progress to such a serious level that any drug treatment should be stopped.
Among patients who are treated with chemotherapy, a large number of patients suffer from mucositis although the severity thereof may differ. So, there is a great need to develop an effective and simple method for treating stomatitis. Conventionally, stomatitis is treated by oral cleansing or administration with various kinds of vitamins. Specifically, stomatitis caused by a chemotherapeutic or radioactive treatment can be treated by mouth wash administration of allopurinol or sodium alginate (Archives, Vol. 55, No. 1:28, 1995; Japanese Journal of Hospital Pharmacy, Vol. 18, No. 5:510, 1992; Japanese Journal of Nursing Acts, Vol. 37, No. 15:44, 1991; The Journal of Japanese Society for Cancer Therapy, Vol. 25, No. 6:1129, 1990). However, such a mouth wash administration shows low effectiveness in alleviating symptoms, is ineffective for serious stomatitis, and requires a long administration period to obtain any improvement in symptoms. Due to these problems, there have been many efforts to develop a drug or method for treating stomatitis which shows a high curative effect in a short period of time.
Most conventional compositions for treating stomatitis are prepared in ointments or patches which contain an adhesive polymer. For example, U.S. Pat. No. 56,578,310 discloses a bioadhesive ointment formed of an emulsion containing mineral oil, hydroxyl propyl methyl cellulose, and the like; and Korean Patent Application Pub. No. 1994-0023469 discloses plasters having a double film structure containing a steroid drug and a method of preparing the same.
As for other forms excluding ointments or patches, US Patent Application Pub. No. 2002/0219634 discloses a bioadhesvie solution or suspension having a viscosity ranging from 50-50,000 cps, and Korean Patent Application Pub. No. 2005-55858 discloses a drug delivery system for oral cavity in the form of a liquid or gel drug including a mixture of a hydrophilic polymer and a water-insoluble polymer.
Meanwhile, International Publication No. WO 03/95637 discloses use of an epidermal growth factor for treating stomatitis. The epidermal growth factor which is known as urogastrones is a polypeptide having a molecular weight of 6045 with 53 amino acids and three disulfide bonds. The epidermal growth factor stimulates mitosis and cell growth of various kinds of cells, such as an epithelial cell or a mesenchymal cell, and hinders gastric acid secretory, and thus, the epidermal growth factor is effective in treating a gastric ulcer or a wound on skin or a cornea (Carpenter, Experimental Cell Research, 164:1-10, 1986). Accordingly, if the epidermal growth factor is formulated together with an adhesive polymer, such as hydroxypropyl methyl cellulose, high effectiveness in treating stomatitis can be obtained.
This method, however, is inconvenient and can cause a second infection because ointments or patches which contain the epidermal growth factor and the adhesive polymer should be directly applied or attached to an oral inflammation or a wound by a patient. To avoid these problems, the epidermal growth factor and the adhesive polymer can be prepared in a liquid type and then formulated in a spray form. The liquid formulation method, however, decreases stability of the epidermal growth factor due to use of an aqueous medium in which molecules move relatively more actively.